Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Anti-GD2 3F8 Monoclonal Antibody and GM-CSF for High-Risk Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02100930
• Other study ID #: 13-260
• Status: Completed
• Phase: N/A
• Start date: March 2014
• Est. completion date: March 7, 2019

Study information

• Verified date: April 2019
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to be able to supply an experimental combination of drugs called 3F8 and GM-CSF (also called sargramostim) to patients with high-risk neuroblastoma who may benefit from treatment.

Description:

This treatment uses 3F8/GM-CSF and isotretinoin for: Group 1 patients are in 1st CR/VGPR; Group 2 patients are in a ≥2nd CR/VGPR; and Group 3 patients have primary refractory NB in BM. All patients will receive 3F8/GM-CSF through 24 months.

Road Map/Schema for Group 1 (1st CR/VGPR) and Group 2 (≥2nd CR/VGPR) patients:

Cycle 1 3F8 (iv) + GM-CSF subcutaneous (sc) (1 wk) 2-4-wk interval Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8. * assessment of BM status by standard histology

Road Map/Schema for Group 3 patients (BM positive): The break between end of a cycle of 3F8/GM-CSF and start of next cycle is approximately 2-to-4-weeks through 4 cycles after achievement of CR in BM; subsequent breaks are ~6-8 weeks. Please see roadmap below for a patient achieving CR in BM after cycle 1. Cycle 1 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - BM negative Cycle 2 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval* - oral isotretinoin x14 days Cycle 3 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 4 3F8 (iv) + GM-CSF (sc) (1 wk) 2-4-wk interval - oral isotretinoin x14 days Cycle 5 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days Cycle 6 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval - oral isotretinoin x14 days on, 14 days off, 14 days on (6th cycle) Cycle 7 3F8 (iv) + GM-CSF (sc) (1 wk) 6-8-wk interval Continue with 6-8-wk intervals through 24 months from 1st dose of 3F8.

• assessment of BM response by standard histology

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: March 7, 2019
• Est. primary completion date: March 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of NB as defined by international criteria,62 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels.

• High-risk NB, as defined by risk-related treatment guidelines and the International NB Staging System, i.e., stage 4 with (any age) or without (>18 months) MYCNamplification, 63 or MYCN-amplified NB other than stage 1.64,65

• Patients are in CR/VGPR or have primary refractory NB in BM - i.e., NB resistant to standard therapy, as evidenced by persistence of NB in BM by histology or MIBG scan, but all other findings in scans show VGPR.

• Children and adults are eligible.

• Signed informed consent indicating awareness of the scheduling and side effects, as well as testing requirements, of this program.

Exclusion Criteria:

• Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3, except for grade 3 hematologic toxicity.

• Progressive disease (PD)

• History of allergy to mouse proteins.

• Active life-threatening infection.

• Human anti-mouse antibody (HAMA) titer >1000 Elisa units/ml.

• Pregnant women

• Inability to comply with protocol requirements.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• Anti-GD2 3F8 Monoclonal Antibody

Drug:
• GM-CSF (granulocyte-macrophage colony-stimulating factor)

• oral isotretinoin

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Therapeutic Response	Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: >50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: <50% decrease in all tumor markers; Progressive disease (PD): new lesion, or >25 % increase in any disease marker.	2 years
Primary	Complete Remission	Disease status is defined by the International Neuroblastoma Response Criteria - Complete response/remission (CR): NED; Partial response/remission: >50% decrease in all disease parameters, exceptbone scan unchanged or improved; no more than 1 positive bone marrow site; Stable disease: <50% decrease in all tumor markers; Progressive disease (PD): new lesion, or >25 % increase in any disease marker.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center